Year: 2020
Type: article
Abstract: The neural substrates of insomnia/hyperarousal induced by stress remain unknown. Here, we show that restraint stress leads to hyperarousal associated with strong activation of corticotropin-releasing hormone neurons in the paraventricular nucleus of hypothalamus (CRH PVN ) and hypocretin neurons in the lateral hypothalamus (Hcrt LH ). CRH PVN neurons are quiescent during natural sleep-wake transitions but are strongly active under restraint stress. CRISPR-Cas9-mediated knockdown of the crh gene in CRH PVN neurons abolishes hyperarousal elicited by stimulating LH-projecting CRH PVN neurons. Genetic ablation of Hcrt neurons or crh gene knockdown significantly reduces insomnia/hyperarousal induced by restraint stress. Given the association between stress and immune function, we used single-cell mass cytometry by time of flight (CyTOF) to analyze peripheral blood and found extensive changes to immune cell distribution and functional responses during wakefulness upon optogenetic stimulation of CRH PVN neurons. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRH PVN circuitry.
Source: Science Advances
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G2081256432, G2857676244, G3390042078, G3413614710, Arousal circuitry and opiate-associated memories, G3739355248, G4417220376, Investigating the hypocretin to VTA circuit in memory consolidation during sleep, G5302847751, G6279284837, G9000028589, G9000138777, G9000224250, G9000229809, G9000338143
OpenAlex ID: W3084090169